Oncotarget

Research Papers:

Platelet activation parameters and platelet-leucocyte-conjugate formation in glioblastoma multiforme patients

Sascha Marx _, Maximilian Splittstöhser, Frederik Kinnen, Eileen Moritz, Christy Joseph, Sebastian Paul, Heiko Paland, Carolin Seifert, Madlen Marx, Andreas Böhm, Edzard Schwedhelm, Kerstin Holzer, Stephan Singer, Christoph A. Ritter, Sandra Bien-Möller, Henry W.S. Schroeder and Bernhard H. Rauch

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Oncotarget. 2018; 9:25860-25876. https://doi.org/10.18632/oncotarget.25395

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Abstract

Sascha Marx1, Maximilian Splittstöhser1,2, Frederik Kinnen1, Eileen Moritz2, Christy Joseph2, Sebastian Paul5, Heiko Paland1,2, Carolin Seifert1,2, Madlen Marx4, Andreas Böhm2, Edzard Schwedhelm6, Kerstin Holzer7, Stephan Singer7, Christoph A. Ritter3, Sandra Bien-Möller1,2, Henry W. S. Schroeder1 and Bernhard H. Rauch2

1Department of Neurosurgery, University Medicine Greifswald, Greifswald, Germany

2Department of Pharmacology, Center of Drug Absorption and Transport (C_DAT), University of Medicine Greifswald, Greifswald, Germany

3Clinical Pharmacy, Institute of Pharmacy, University of Greifswald, Greifswald, Germany

4Department of Paediatric Oncology and Haematology, University Medicine Greifswald, Greifswald, Germany

5Department of Ophthalmology, University Medicine Greifswald, Greifswald, Germany

6Institute of Clinical Pharmacology and Toxicology, University Medical Center, Hamburg, Germany

7Institute of Pathology, University Medicine Greifswald, Greifswald, Germany

Correspondence to:

Sascha Marx, email: marxs@uni-greifswald.de

Keywords: platelet activation; glioblastoma multiforme; P-selectin; sphingosine-1-phosphat; PSGL-1

Received: November 22, 2017     Accepted: April 28, 2018     Published: May 25, 2018

ABSTRACT

Patients with glioblastoma multiforme (GBM) suffer from an increased incidence of vascular thrombotic events. However, key influencing factors of the primary hemostasis have not been characterized in GBM patients to date. Thus, the present study determines the activation level of circulating platelets in GBM patients, in-vitro reactivity to agonist-induced platelet stimulation and the formation of circulating platelet-leucocyte conjugates as well as the plasma levels of the proinflammatory lipid mediator sphingosine-1-phosphate (S1P). The endogenous thrombin potential (ETP) was determined as global marker for hemostasis.

The 21 GBM patients and 21 gender and age matched healthy individuals enrolled in this study did not differ in mean total platelet count. Basal surface expression of platelet CD63 determined by flow cytometry was significantly increased in GBM patients compared to controls as was observed for the concentration of soluble P-selectin in the plasma of GBM patients. While the ETP was not affected, the immunomodulatory lipid S1P was significantly decreased in peripheral blood in GBM. Interestingly, monocyte expression of PSGL-1 (CD162) was decreased in GBM patient blood, possibly explaining the rather decreased formation of platelet-monocyte conjugates.

Our study reveals an increased CD63 expression and P-selectin expression/ secretion of circulating platelets in GBM patients. In parallel a down-modulated PSGL-1 expression in circulating monocytes and a trend towards a decreased formation of heterotypic platelet-monocyte conjugates in GBM patients was seen. Whether this and the observed decreased plasma level of the immunomodulatory S1P reflects a systemic anti-inflammatory status needs to be addressed in future studies.


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